Point-of-care testing (POCT) is defined as medical testing at or near the site of patient care, for example at the doctor's office. Point of Care Testing systems enable quick performance of tests, for example blood tests, eliminating a need for sending samples to laboratory. Quick obtaining of test results allows immediate clinical management decisions to be made.
It is desirable that such POCT systems be simple to use and require minimal maintenance. To that end, some systems use fully self-contained disposable cartridges or strips. In fully-automated systems, no preliminary sample preparation is required and the cartridges eliminate the risk of contamination.
U.S. Pat. No. 7,347,617 by Pugia et al., entitled “Mixing in Microfluidic Devices”, published in 2008, discloses mixing of liquids in a microfluidic device, by dispensing the liquids into a first chamber to produce combined liquid. The liquids are thereafter discharged through at least one capillary from the first chamber into a second chamber for complete mixing.
U.S. Pat. No. 4,030,888 by Yamamoto et al., entitled “Automatic Blood Analyzer”, published in 1977, discloses a fully automatic system for determining the seven blood parameters. The flow of a diluent and the blood solution starting from the introduction of the sample, to counting portions, means for determination, and to the outlets are controlled by the supply of either vacuum or pneumatic pressure into two rotary proportioning cocks and chambers positioned upstream or downstream thereof.
U.S. Pat. No. 4,826,775 by Burns et al., entitled “Dilution Apparatus and Method”, published in 1989, discloses an automatic dilution apparatus and method operable in conjunction with automated sample liquid analysis systems to automatically dilute sample liquids as supplied thereby to automated sample liquid analysis apparatus.
U.S. Pat. No. 4,908,187 by Kipke et al., entitled “Multi-Chambered Pump-Valve Device”, published in 1990, discloses a diluting and mixing device which is capable of diluting a first solution to produce a second solution which is mixed with an undiluted third solution, to reproducibly produce a unique series of combined solutions. Each solution in said series of combined solutions may vary only in the concentration of a single (selected) reactant, and typically, each successive solution becomes increasingly more concentrated in the selected reactant. By employing a modification in procedure, each successive solution in said series may become decreasingly less concentrated in the selected reactant. This invention further relates to an automated system comprising the device connected to a stepping motor so as to rapidly and reproducibly produce said series of solutions, said device being further connected to an analyzer means for obtaining chemical, biochemical, or physical chemical data on said series of solutions.
U.S. Pat. No. 5,350,693 by Maimon et al., entitled “Multichamber Syringe Device for Fusing Cells”, published in 1994, discloses an apparatus for fusing cells which includes a multichamber syringe having a first chamber containing a suspension of cells, a second chamber containing a suspension of cells, and a third chamber containing at least 40% by volume polyethylene glycol (PEG). The exit passageways of the chambers being braided such that the downstream ends thereof are beveled and face one another at the same level. The relative cross sections of the chambers being of a diameter such that a desired ratio of the suspensions and solution form in midair a mixture of 15% to 25% PEG by volume. The apparatus also includes a non-linear tube in fluid communication with the syringe for receiving the mixture therefrom and a device for causing a reciprocating passage of the mixture through the non-linear tube.
U.S. Pat. No. 5,380,491 by Carver Jr. et al., entitled “Apparatus for Pumping and Directing Fluids for Hematology Testing”, published in 1995, discloses an apparatus for hematology testing, which has a sensing unit defining a counting orifice for the flow of a blood sample through the counting orifice to analyze the blood sample, and a pump unit having three syringes. A first syringe is coupled in fluid communication with the sensing unit on the inlet, side of the counting orifice for injecting a stream of blood sample through the counting orifice. A second syringe is coupled in fluid communication with the sensing chamber on the inlet side of the counting orifice for simultaneously injecting a sheath of fluid surrounding the sample stream on the inlet side of the counting orifice. A third syringe is coupled to the sensing chamber on the outlet side of the counting orifice for aspirating a sheath of fluid from the sensing chamber surrounding the sample stream on the outlet side of the counting orifice.
U.S. Pat. No. 5,840,254 by Carver Jr. et al., entitled “Apparatus for Mixing Fluids for Analysis”, published in 1998, discloses an apparatus for fluid analysis, such as hematologic analysis, a plurality of reagent-mixture components are each injected by a respective pump through a valve matrix and into a flow-injection unit. The flow-injection unit defines a mixing chamber including a plurality of protuberances or nubs projecting inwardly toward the center of the chamber, and spaced relative to each other both axially and radially. As the reagent-mixture components are injected into the mixing chamber, the nubs agitate the fluid flow and create turbulence, thereby dispersing the reagent-mixture components and in turn mixing the components together to create a reagent mixture. The flow rates of the reagent-mixture components are adjusted in order to select the reagent-mixture ratio as the components are combined in the flow-injection unit to thereby create the selected reagent mixture. Upon passage through the flow-injection unit, the reagent mixture is injected into a sensing unit for analyzing a particle distribution of the mixture.
U.S. Pat. No. 6,241,379 by Larsen et al., entitled “Micromixer Having a Mixing Chamber for Mixing two Liquids Through the Use of Laminar Flow,” published in 2001, discloses a micromixer having a mixing chamber for mixing two fluids. The mixing chamber has a first inlet arrangement for the supply of a first fluid and a second inlet arrangement for the supply of a second fluid. The mixing chamber includes a wall along which the first fluid flows, and the second inlet arrangement has at least one opening in the wall. A projection is located on the wall adjacent to the opening and extending into the mixing chamber so that the first fluid flows around the projection and builds a boundary layer with the second fluid. Mixing takes place by diffusion through the boundary layer.
U.S. Pat. No. 6,537,813 by Chen et al., entitled “Concurrent Flow Mixing Methods and Apparatuses for the Preparation of Gene Therapy Vectors and Compositions Prepared Thereby”, published in 2003, discloses methods adapted for making mixtures and condensate compositions. In the various embodiments, it provides controlled and uniform mixing of gene therapy vectors and gene therapy vector vehicles for improved reproducibility, scaleability, stability, and pharmaceutical efficacy.
U.S. Pat. No. 6,820,506 by Kipke et at, entitled “Multi-Chambered Pump-Valve Device”, published in 2004, discloses a multi-chambered pump-valve device for performing chemical processes, detections or analyses is described herein. The device includes a plurality of chambers having variable volumes in fluid communication with one another via one or more passageways. Liquid may be directed through the device by merely changing the volumes of two or more chambers.
U.S. Pat. No. 6,877,892 by Karp et al., entitled “Multi-Stream Microfluidic Aperture Mixers”, published in 2005, discloses a robust microfluidic mixing devices that mix multiple fluid streams passively, without the use of moving parts. In one embodiment, these devices contain microfluidic channels that are formed in various layers of a three-dimensional structure. Mixing may be accomplished with various manipulations of fluid flow paths and/or contacts between fluid streams.
U.S. Pat. No. 6,915,713 by Kipke et al., entitled “Multi-Chambered Pump—Valve Device”, published in 2005, discloses a multi-chambered pump—valve device for performing chemical processes, detections or analyses. The device includes a plurality of chambers having variable volumes in fluid communication with one another via one or more passageways. Liquid may be directed through the device by merely changing the volumes of two or more chambers.
U.S. Pat. No. 6,979,569 by Carver Jr. et al., entitled “Apparatus and Method for Mixing Fluids for Analysis”, published in 2005, discloses an apparatus for fluid analysis, a plurality of reagent-mixture components are each injected by a respective pump through a valve matrix and into a flow-injection unit. The flow-injection unit defines a mixing chamber including a plurality of. As the reagent-mixture components are injected into the mixing chamber, the nubs agitate the fluid flow, thereby dispersing the reagent-mixture components and in turn mixing the components together to create a reagent mixture. The flow rates of the reagent-mixture components are adjusted in order to select the reagent-mixture ratio as the components are combined in the flow-injection unit to thereby create the selected reagent mixture. Upon passage through the flow-injection unit, the reagent-mixture is injected into a sensing unit for analyzing a particle distribution of the mixture.
U.S. Pat. No. 7,314,060 by Chen et al., entitled “Fluid Flow Conducting Module”, published in 2008, discloses a fluid flow conducting module comprising two or more inlets, one or more outlets, and a chamber that has a first and second blocks therein. Further, the chamber has a gradually wider section in the middle, and two convergent ends. One convergent end is connected to the inlets, and the other convergent end is connected to the outlets. The fluids are injected into the chamber through the inlets, flow through the chamber, and conducted towards one or more outlets for further collection and analysis.
PCT Publication WO/2009/053928 by Shany et al., entitled “Cartridge for a Biological Sample”, published in 2009, discloses a sealed removable cartridge adapted for insertion into an assay device and adapted to contain a biologic sample, the cartridge comprising two or more assay locations adapted to facilitate, within said cartridge, two or more assays of said biologic sample; and an actuator interface adapted to interface with an actuator of said assay device, to transport said biologic sample towards at least one of said assay locations.
U.S. Pat. No. 5,096,669 by Lauks et al., entitled “Disposable sensing device for real time fluid analysis”, published in 1992, discloses a system comprising a disposable device and hand held reader, which can perform a variety of electrochemical measurements on blood or other fluids. In operation, a fluid sample is drawn into the disposable device through an orifice by capillary action. The orifice is sealed off and the disposable device is inserted into the reader. The reader which controls the test sequence and flow of fluid causes a calibrant pouch located inside the device to be pierced, releasing the calibrant fluid to flow across the sensor arrays to perform calibration. Next an air bladder located in the device is depressed, forcing the sample across the sensors where measurements are performed and read by the reader which performs the calibrations. Once the measurements are made, the device can be withdrawn from the reader and discarded.
PCT Patent Application WO/2003/044488 by Berndtsson, entitled “Disposable apparatus for use in blood testing”, published in 2003, discloses a disposable apparatus for use in blood testing adapted for simultaneous dilution of a blood sample into two different dilution ratios. A block-shaped housing has a first and a second receptacle; a first and a second cylinder, each having a piston moveable therein and each containing a defined volume of a diluent a valve including a valve body having three valve body channels extending therethrough and being positionable in three distinct positions. In one position the receptacles are put in simultaneous communication with one each of the cylinders through pairs of the channels. One of the receptacles as a first means for receiving a blood sample, is adapted to receive a blood sampling capillary tube.
PCT Patent Application WO/2003/104772 by Larsen, entitled “A disposable cartridge for characterizing particles suspended in a liquid” published in 2003, discloses a disposable cartridge for characterizing particles suspended in a liquid, especially a self-contained disposable cartridge for single-use analysis, such as for single-use analysis of a small quantity of whole blood. The self-contained disposable cartridge facilitates a straightforward testing procedure, which can be performed by most people without any particular education. Furthermore, the apparatus used to perform the test on the cartridge is simple, maintenance free, and portable.
PCT Patent Application WO/2006/084472 by Larsen entitled “Dual sample cartridge and method for characterizing particle in liquid” published in 2006, discloses an apparatus for characterizing particles suspended in a liquid, especially a self-contained disposable cartridge for single-use analysis, such as for single-use analysis of a small quantity of whole blood. Furthermore, the present invention relates to a method for characterizing particles in liquid and a device for sampling a small and accurate volume of liquid. The apparatus comprises a housing having a mixing chamber and a collection chamber separated by a wall containing an opening, a first bore in the outer surface of the housing for entrance of a liquid sample, a first cavity for receiving and holding a first liquid sample, and a second cavity for receiving and holding a second liquid sample.
U.S. Pat. No. 6,016,712 by Warden and Kaplan, entitled “Device for receiving and processing a sample”, published in 2000, discloses a device for receiving and processing a sample. The device comprises a sample receiving element adapted to establish fluid communication with and receive a sample directly from a sample container. The sample receiving element also allows for introduction of a sample into the device. A first chamber is in fluid communication with the sample receiving element. One or more second chambers are in fluid communication with the first chamber. The device also comprises first and second ports. The first port provides for venting the device. The second port provides for establishing communication between the device and means for moving the sample from the sample receiving element to the first chamber and for moving the sample from the first chamber to the one or more second chambers. Also included as part of the device is means for controlling the precise amount of the sample introduced into each of the second chambers. The first chamber and/or one or more of the second chambers are adapted for processing the sample. Also disclosed are kits containing the above devices and methods of using the devices to process a sample.
United States Patent Application 2006/0257993 by Mcdevitt et al., entitled “Integration of fluids and reagents into self-contained cartridges containing sensor elements”, published in 2006, discloses an analyte detection device and method related to a portable instrument suitable for point-of-care analyses. In some embodiments, a portable instrument may include a disposable cartridge, an optical detector, a sample collection device and/or sample reservoir, reagent delivery systems, fluid delivery systems, one or more channels, and/or waste reservoirs. Use of a portable instrument may reduce the hazard to an operator by reducing an operator's contact with a sample for analysis. The device is capable of obtaining diagnostic information using cellular- and/or particle-based analyses and may be used in conjunction with membrane- and/or particle-based analysis cartridges. Analytes, including proteins and cells and/or microbes may be detected using the membrane and/or particle based analysis system.
United States Patent Application 2009/0215072 by Mcdevitt et al., entitled “Methods and compositions related to determination and use of white blood cell counts” published in 2009, discloses an analyte detection device and method related to a portable instrument suitable for point-of-care analyses. In some embodiments, a portable instrument may include a disposable cartridge, an optical detector, a sample collection device and/or sample reservoir, reagent delivery systems, fluid delivery systems, one or more channels, and/or waste reservoirs. Use of a portable instrument may reduce the hazard to an operator by reducing an operator's contact with a sample for analysis. The device is capable of obtaining diagnostic information using cellular- and/or particle-based analyses and may be used in conjunction with membrane- and/or particle-based analysis cartridges. Analytes, including proteins and cells and/or microbes may be detected using the membrane and/or particle based analysis system.
PCT Publication WO/2008/149365 by Leshansky et al., entitled “Systems and Methods for Focusing Particles”, published in 2008, discloses a method of focusing particles. The method includes: providing a suspension of the particles in a suspending medium; and flowing the suspension along a channel, such that the flowing suspension occupies a certain volume that has at least one cross-sectional dimension smaller than 100 μm. The suspending medium has such viscoelastic properties, that flowing the suspension in the channel directs at least some of the particles towards a focus region, enclosed in said certain volume.
PCT Publication WO/2010/013238, by Bransky et al., entitled “Microfluidic System and Method for Manufacturing the Same”, published in 2010, discloses a microfluidic system. The microfluidic system comprises a microchannel having in fluid communication with a fluid inlet for receiving a first fluid. The microfluidic system can further comprise a piezoelectric actuator which controls the flow of the first fluid in the microchannel by selectively applying external pressure on the wall of the microchannel.